Environmental stress can induce an increase in the rate of synthesis of so-called heat shock, or stress, proteins in both procaryotic and eucaryotic cells [see for example Schlesinger et al (eds) in Heat Shock from Bacteria to Man, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1972)]. Although the function of stress proteins has yet to be finally resolved, some have been reported to participate in assembly and structural stabilisation of certain cellular and viral proteins, and their presence at high concentration may have an additional stabilising effect during exposure to adverse conditions.
Many pathogenic organisms have been shown to produce stress proteins [see for example Young D., et al, Proc. Natl. Acad. Sci. USA, 85, 4267-4270 (1988)]. The proteins are thought to be produced in response to the stress of infection to help protect the invading pathogen. Thus, for example, the ability to produce stress proteins has been implicated in the survival of bacterial pathogens within macrophages [Christmas, M. F., et al, Cell, 41, 753-762 (1985) and Morgan R. W., et al, Proc. Natl. Acad. Sci. U.S.A. 83, 8059-8063 (1986)]. It has been suggested that the presence of stress proteins in a variety of human pathogens indicates that the stress response is a general component of infections, and that stress proteins should be considered among candidates for subunit vaccines [Young, D. et al ibid].
The Coryneform bacteria are common inhabitants of healthy human skin and mucous membranes. Some are known pathogens, for example the type species Corynebacterium diphtheriae causes diphtheria in man. Another species, Corynebacterium jeikeium causes septicaemias in neutropenic patients [see for example, Hande, K. R., et al, Ann. Intern. Med., 85, 423-426 (1976)], and C. jeikeium infection has been associated with endocarditis [Jackman, F. J., et al, Syst. Appl. Microbial., 9, (1-2), 83-90 (1987)]. These C. jeikeium species are characterised by being catalase-positive, oxidase-negative, fermentative Gram positive aerobic rods which do not reduce nitrate [Riley, P. S., et al, J. Clin. Microbial., 9, 418-424, (1979)]. They differ from other coryneforms by being highly resistant to antibiotics, including ampicillin, cephalothin, chloramphenicol, erythromycin, gentamicin, penicillin G, streptomycin and tetracycline [Jackman, P. J., Pelczynaka, S., J. Gen. Microbial., 132, (Pt.7), 1911-1915 (1986)].
Conventional therapy for a C. jeikeium infection is systemic vancomycin, which is potentially nephrotoxic. This mitigates against its blind use in pyrexial neutropenic patients, so that it has become important to develop a marker of C. jeikeium infection. There is also a need for a method of treating C. jeikeium infection, particularly in neutropenic patients, which avoids the damaging side effects associated with conventional therapy.